Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.

中文翻译：

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Demethylzeylasteral (T-96) 通过诱导 ROS 介导的 ER 应激和抑制自噬通量启动针对前列腺癌细胞的外在细胞凋亡

Demethylzeylasteral (T-96) 是一种从雷公藤 Hook F (TWHF) 中提取的具有药理活性的三萜单体，据报道它对多种类型的癌细胞具有抗肿瘤作用。然而，T-96 对人前列腺癌 (CaP) 细胞的潜在抗肿瘤作用和可能的潜在机制尚未得到很好的研究。在目前的研究中，T-96 在体外对 CaP 细胞产生显着的细胞毒性，并以剂量​​依赖性方式诱导细胞周期停滞在 S 期。从机制上讲，T-96 通过诱导 ROS 介导的内质网 (ER) 应激促进自噬的启动，但抑制自噬通量，随后激活 CaP 细胞中的外在凋亡途径。这些发现表明，T-96 诱导的内质网应激激活了半胱天冬酶依赖性细胞凋亡途径，从而抑制了 CaP 细胞的增殖。此外，我们观察到 T-96 增强了 CaP 细胞对化疗药物顺铂的敏感性。总之，我们的数据表明 T-96 是一种新型的内质网应激和自噬调节剂，并且在临床上具有针对 CaP 的潜在治疗应用。